title: Solid lipid nanoparticles carrying chemotherapeutic drug across the blood-brain barrier through insulin receptor-mediated pathway.
abstract: Carmustine (BCNU)-loaded solid lipid nanoparticles (SLNs) were grafted with 83-14 monoclonal antibody (MAb) (83-14 MAb/BCNU-SLNs) and applied to the brain-targeting delivery. Human brain-microvascular endothelial cells (HBMECs) incubated with 83-14 MAb/BCNU-SLNs were stained to demonstrate the interaction between the nanocarriers and expressed insulin receptors (IRs). The results revealed that the particle size of 83-14 MAb/BCNU-SLNs decreased with an increasing weight percentage of Dynasan 114 (DYN). Storage at 4 °C for 6 weeks slightly deformed the colloidal morphology. In addition, poloxamer 407 on 83-14 MAb/BCNU-SLNs induced cytotoxicity to RAW264.7 cells and inhibited phagocytosis by RAW264.7 cells. An increase in the weight percentage of DYN from 0% to 67% slightly reduced the viability of RAW264.7 cells and promoted phagocytosis. Moreover, the transport ability of 83-14 MAb/BCNU-SLNs across the blood-brain barrier (BBB) in vitro enhanced with an increasing weight percentage of Tween 80. 83-14 MAb on MAb/BCNU-SLNs stimulated endocytosis by HBMECs via IRs and enhanced the permeability of BCNU across the BBB. 83-14 MAb/BCNU-SLNs can be a promising antitumor drug delivery system for transporting BCNU to the brain.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi , Taiwan, Republic of China. chmyck@ccu.edu.tw
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Shih-Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002330:Carmustine / Q000008:administration & dosage / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011972:Receptor, Insulin; D002330:Carmustine